Substance use disorders (SUD) are highly prevalent and result in substantial disability, morbidity, and premature mortality. Research supported by the parent grant of this application (R01DA0191606) has helped to define risk factors for SUD. Known risk factors for SUD span family history, poor parenting, traumatic experiences, personality traits, and recent stressful life events, early-onset substance use, social deviance and availability of substances. Despite impressive recent progress on the identification of risk factors for SUD, no explicit model has been developed and tested that defines the interrelationships among these variables. Consistent with NIDA's Five Year Strategic Plan's Prevention Priorities 1 To identify the characteristics and patterns of drug abuse and 2 To understand how genes, environment, and development influence the various risk and protective factors for drug abuse, and Cross-Cutting Priority 2 To decrease health disparities related to drug addiction, in this competing renewal, we seek to build a theory-driven, comprehensive model of SUD and examine its invariance across substances, race, and gender. We will use data from the 34,653 participants in Waves 1 and 2 of the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC). Three complementary families of statistical techniques (GLM, Oaxaca-type decompositions and structural equation models) will be applied to guide development of a conceptual model based on the pioneering research of Professor Kendler that focused on risk factors for major depressive disorder, and that we have modified (e.g., by including availability of drugs) to study the etiology and course of SUD. This modified Kendler model provides a comprehensive integration of variables from five developmental stages: childhood, early adolescence, late adolescence, adulthood, and the last year. The risk factors for this model were assessed in all NESARC participants and are widely considered to apply to SUD. Importantly, many of the risk factors are modifiable and amenable to change through prevention and treatment interventions. We propose to use the modified Kendler conceptual model to examine the following aims: 1) To investigate the relationship between risk factors and prevalence of substance use and SUD~ 2) To determine the relationship between risk factors and transition from use to SUD, remission of SUD, and relapse~ 3) To examine whether gender and racial/ethnic differences across the course of SUD are due to the differential distribution or differential effect of the risk factors~ and, 4) To develop and test models of substance use, SUD, transition from SUD, remission from SUD, and relapse. At the conclusion of this study, we will have developed and tested a model that integrates a broad range of risk factors for the onset and course of SUD. These models will help to inform the development and targeting of evidence-based prevention and treatment interventions for SUD.